POS0339 HIGH-GRADE SYNOVITIS ASSOCIATES WITH CLINICAL MARKERS AND RESPONSE TO DMARDS THERAPY IN CHRONIC INFLAMMATORY ARTHRITIS: POST HOC ANALYSIS OF A PROSPECTIVE STUDY
Authors: C. Garaffoni, I. Calciolari, M. Tamussin, M. S. Ciliento, G. Lanza, A. Bortoluzzi, M. Govoni, C. A. Scirè, E. Silvagni
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Inflammatory arthritis (IA), such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), are characterized by the presence of chronic synovitis. The Krenn synovitis score (KSS), a semi-quantitative histopathological score, allows the discrimination between high-grade and low-grade synovitis [1]. Although KSS could be potential useful for profiling patients with IA, its associations with clinical and treatment features are not yet thoroughly described. <h3>Objectives</h3> The aim of this post hoc analysis was to identify clinical and instrumental correlates of KSS and to evaluate the association between high-grade synovitis and treatment response in a prospective cohort of IA including both RA and PsA patients. <h3>Methods</h3> Clinical, laboratory and ultrasound (US) data were retrieved from RA and PsA patients recruited in MATRIX cohort. Inclusion criteria were age ≥18 years, RA (ACR/EULAR 2010) or PsA (CASPAR criteria) diagnosis, presence of active disease with eligibility to start/modify new DMARDs therapy. Patients underwent US-guided synovial biopsy of one of the most involved joint (knee or wrist) before starting/modifying DMARDs treatment according to treat-to-target strategy. The samples were analysed by an expert pathologist and KSS was calculated. Univariate and multivariate logistic regression analyses were performed to evaluate the relation between KSS and baseline variables. The association between KSS and treatment response, defined by ACR20, DAS28 remission and the newest ACR/EULAR remission criteria (2) at 6 months of follow-up, was investigated in univariate logistic regression analysis. <h3>Results</h3> 50 patients, 31 RA and 19 PsA, completed 6 months of follow-up after synovial biopsy. Baseline characteristics did not differ between RA e PsA patients except for F/M ratio (77% vs 32%, p=0.001). Four patients (8%) were treatment-naïve and, within the refractory patients (46/50, 92%), 19 (38%) were previously treated with b/tsDMARDs. GCs exposure was reported for 17/31 (55%) RA and 8/19 (42%) PSA patients. KSS was available for 47 patients and the median value was 6.00 (IQR 4.00-7.00) in RA samples and 4.00 (IQR 3.00-5.75) in PsA. Inflammatory infiltrates score was significantly higher in RA than in PsA patients (median 3.00 vs 2.00, p=0.034)(Figure 11A). At univariate analysis, the presence of C reactive protein (CRP)≥0.5 mg/dl, erythrocyte sedimentation rate (ESR)≥30 mm, DAS28-ESR, joint stiffness in the biopsied joint (VAS≥60 mm), moderate to high synovial effusion and moderate to high power Doppler signal detected by US at baseline evaluation in the biopsied joint all associated with increased risk of high-grade synovitis. Fibromyalgia, instead, associated with a reduced risk of high-grade synovitis. At multivariate analysis, US effusion (OR 7.18, 95%CI 1.49, 47.98), CRP (OR 5.66, 95%CI 1.23, 33.22) and joint stiffness (OR 7.67, 95%CI 1.31, 73.51) significantly associated with high-grade KSS (Figure 1B). After 24 weeks (33/50 new b/tsDMARDs, 6/50 new csDMARDs initiated), 24/48 patients achieved DAS28 remission, 18/48 ACR/EULAR remission and 26/50 ACR20. Univariate analysis revealed increased OR of remission/response for patients with high-grade synovitis (ACR20 OR 4.57, 95%CI 1.36, 17.01, p=0.017; DAS28 remission OR 5.85, 95%CI 1.60, 25.48, p=0.011; ACR/EULAR OR 7.50, 95%CI 1.69, 53.49, p=0.017) (Figure 1C). The interaction between KSS and diagnosis had no significant impact on the outcome. <h3>Conclusion</h3> KSS is a simple and feasible tool for disease stratification of patients with IA, recommended in synovial biopsy research. In our study, high CRP, joint stiffness and US presence of synovial effusion correlated with the presence of high-grade synovitis. High grade synovitis was associated with increased probability of achieving remission 6 months after therapy upgrade in active IA patients independently from diagnosis. <h3>References</h3> [1]Krenn et al. Histopathology. 2006 Oct;49(4):358-64. [2]Studenic et al. Ann Rheum Dis. 2023 Jan;82(1):74-80. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Carlo Garaffoni: None declared, Ilaria Calciolari: None declared, Marianna Tamussin: None declared, Maria Sofia Ciliento: None declared, Giovanni Lanza: None declared, Alessandra Bortoluzzi Speakers bureau: GSK, Astra-Zeneca, Consultant of: GSK, Astra-Zeneca, Marcello Govoni Speakers bureau: Abbvie, Lilly, Pfizer, Galapagos, Novartis, Consultant of: Abbvie, Lilly, Pfizer, Galapagos, Novartis, Carlo Alberto Scirè Speakers bureau: AbbVie, Novartis and Galapagos, Consultant of: AbbVie, Novartis and Galapagos, Grant/research support from: AbbVie and Lilly, Ettore Silvagni Speakers bureau: AbbVie, Lilly, Galapagos, Amgen, Novartis, Astra-Zeneca, Consultant of: AbbVie, Lilly, Galapagos, Amgen, Novartis, Astra-Zeneca, Grant/research support from: AbbVie and Lilly.